This document summarizes the history and evidence around fluid management and the use of colloids like albumin and hydroxyethyl starch (HES). It discusses several large randomized controlled trials that compared albumin and HES to crystalloids in critically ill patients. The SAFE study found increased mortality with albumin compared to saline in ICU patients. Subsequent trials found increased mortality and renal failure with HES compared to crystalloids in sepsis patients. This led regulatory agencies around the world to restrict or withdraw approval for HES use in high-risk patients like those with sepsis or renal impairment. The evidence suggests colloids like HES may increase mortality and renal failure compared to crystalloid fluids in critically ill patients.
An Updated presentation of the management of severe sepsis including best evidence for fluid resuscitation, vasopressors, blood pressure target, steroid replacement, blood transfusion and other moralities.
Anthony Delaney, an Emergency Physician and Intensivist from Sydney gives an update on Sepsis Resuscitation in 2012. And he doesn't even talk about ARISE!
An Updated presentation of the management of severe sepsis including best evidence for fluid resuscitation, vasopressors, blood pressure target, steroid replacement, blood transfusion and other moralities.
Anthony Delaney, an Emergency Physician and Intensivist from Sydney gives an update on Sepsis Resuscitation in 2012. And he doesn't even talk about ARISE!
This talk is a summary of 4 Objectives:
1. What is the ideal MAP in Sepsis (65 vs 85 mmHg)
2. What is the ideal Hb Transfusion Threshold (7 vs 9 g/dL)
3. SIRS Criteria for Screening of Severe Sepsis
4. Summary and Take Home Messages from the ProCESS, ARISE, & ProMISe Trials
This presentation discusses the latest evidence for blood transfusion triggers in the intensive care unit of various clinical condition including severe sepsis, GI bleed, post surgical cases, and post cardiac surgery among other cnditions
Presentation by Dr Jason Wu - resident in Critical Care at TWH, for the critical care journal club report findings of a paper by Kaukonen KM, et al. N Engl J Med. 2015 & update from the recent SMACC conference in Chicago #FOAMed #SMACC (http://www.ncbi.nlm.nih.gov/m/pubmed/25776936/)
A talk by Max Bell at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine.
All available content from SSAI2017: https://scanfoam.org/ssai2017/
Delivered in collaboration between scanFOAM, SSAI & SFAI.
Lactate has been viewed as a byproduct of anaerobic metabolism and an indicator of tissue hypoperfusion since the 1900s. This theory is still widely believed. Paul busts the myths surrounding lactic acidosis, anaerobic metabolism, tissue hypoxia and the role of lactate in sepsis.
Key take-away facts include:
- The production of lactate actually consumes hydrogen ions. Lactic acidosis is really lactic alkalosis.
- Lactate is produced physiologically and is a precursor for gluconeogenesis.
- During exercise, skeletal muscle exports lactate as the primary fuel for the heart and brain.
- At VO2max, intracellular oxygen stays the same. Anaerobic metabolism in cells only occur as a pre-terminal event. The exception is in complete arterial occlusion.
- Adrenaline promotes lactate production
- Lactate infusion has been shown to increase cardiac output in septic and cardiogenic shock
- Lactate is a survival advantage!
Rapid response systems (RRSs) have become a routine part of the way patients are managed in general wards of acute care hospitals. They have been adopted by national health and safety organisations in North America, Canada, the United Kingdom and Australia and are increasingly being used in other parts of the world.
Studies have almost universally shown significant reductions in outcome indicators such as mortality (up to one third) and cardiac arrest rates (up to 50%). However the validity of these outcomes is questionable as most of these studies are single-centre, before-and-after studies conducted by one or two clinical champions in Rapid Response.
This presentation reveals that the implementation of an Intensivist led Rapid Response Team in an Australian quaternary hospital did not demonstrate such dramatic results. In fact, after one year of service the standardised mortality ratio and the in-hospital cardiac arrest rate remained similar.
The presentation explores some of the operational impacts of a RRS including the replacement of critical thinking with reliance on protocols and the progressive super-specialisation of medical teams. Despite these impacts and relatively static patient outcome data, the service has rapidly become an integral part of the hospital.
Barriers between Intensive Care and ward staff have broken down and quality outcome results have consistently shown ward nurses and doctors feel better prepared, educated and supported in managing clinical deterioration. These surprising results raise the question; should we place more value in quality outcomes?
This talk is a summary of 4 Objectives:
1. What is the ideal MAP in Sepsis (65 vs 85 mmHg)
2. What is the ideal Hb Transfusion Threshold (7 vs 9 g/dL)
3. SIRS Criteria for Screening of Severe Sepsis
4. Summary and Take Home Messages from the ProCESS, ARISE, & ProMISe Trials
This presentation discusses the latest evidence for blood transfusion triggers in the intensive care unit of various clinical condition including severe sepsis, GI bleed, post surgical cases, and post cardiac surgery among other cnditions
Presentation by Dr Jason Wu - resident in Critical Care at TWH, for the critical care journal club report findings of a paper by Kaukonen KM, et al. N Engl J Med. 2015 & update from the recent SMACC conference in Chicago #FOAMed #SMACC (http://www.ncbi.nlm.nih.gov/m/pubmed/25776936/)
A talk by Max Bell at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine.
All available content from SSAI2017: https://scanfoam.org/ssai2017/
Delivered in collaboration between scanFOAM, SSAI & SFAI.
Lactate has been viewed as a byproduct of anaerobic metabolism and an indicator of tissue hypoperfusion since the 1900s. This theory is still widely believed. Paul busts the myths surrounding lactic acidosis, anaerobic metabolism, tissue hypoxia and the role of lactate in sepsis.
Key take-away facts include:
- The production of lactate actually consumes hydrogen ions. Lactic acidosis is really lactic alkalosis.
- Lactate is produced physiologically and is a precursor for gluconeogenesis.
- During exercise, skeletal muscle exports lactate as the primary fuel for the heart and brain.
- At VO2max, intracellular oxygen stays the same. Anaerobic metabolism in cells only occur as a pre-terminal event. The exception is in complete arterial occlusion.
- Adrenaline promotes lactate production
- Lactate infusion has been shown to increase cardiac output in septic and cardiogenic shock
- Lactate is a survival advantage!
Rapid response systems (RRSs) have become a routine part of the way patients are managed in general wards of acute care hospitals. They have been adopted by national health and safety organisations in North America, Canada, the United Kingdom and Australia and are increasingly being used in other parts of the world.
Studies have almost universally shown significant reductions in outcome indicators such as mortality (up to one third) and cardiac arrest rates (up to 50%). However the validity of these outcomes is questionable as most of these studies are single-centre, before-and-after studies conducted by one or two clinical champions in Rapid Response.
This presentation reveals that the implementation of an Intensivist led Rapid Response Team in an Australian quaternary hospital did not demonstrate such dramatic results. In fact, after one year of service the standardised mortality ratio and the in-hospital cardiac arrest rate remained similar.
The presentation explores some of the operational impacts of a RRS including the replacement of critical thinking with reliance on protocols and the progressive super-specialisation of medical teams. Despite these impacts and relatively static patient outcome data, the service has rapidly become an integral part of the hospital.
Barriers between Intensive Care and ward staff have broken down and quality outcome results have consistently shown ward nurses and doctors feel better prepared, educated and supported in managing clinical deterioration. These surprising results raise the question; should we place more value in quality outcomes?
Hemorrhage is the leading cause of preventable death following trauma. Non-compressible hemorrhage is of particular concern as these patients require emergent intervention and many will die prior to anatomic hemostasis. For years, left anterior thoracotomy, the “ED thoracotomy”, was the standard of care for temporary proximal aortic occlusion, but survival remained dismal. Endoluminal aortic occlusion which was actually first described in the 1950s. With the increasing use of endovascular therapies for a wide variety of vascular disease, the “REBOA” (Resuscitative Endovascular Balloon Occlusion of the Aorta) began to be reported for use for ruptured abdominal aneurysms in the 2000s. Since that time, interest in its use in trauma has been increasing with a variety of basic science studies and early clinical series and case reports documenting potential benefits. Although no large randomized trials, or even large observational studies, are available, use of the REBOA is considered standard of care in many centers. Typically the REBOA is placed via the femoral artery either percutaneously or via a cut down and the aorta is occluded with a balloon placed over a wire by standard Seldinger-type technique. The balloon can be placed in “zone 1” just above the diaphragm to provide occlusion to the abdominal viscera and pelvic vasculature or in “zone 3” at the aortic bifurcation to provide inflow control to the pelvis and lower extremities. Injuries are then addressed and the balloon is carefully deflated taking care to avoid metabolic collapse from reperfusion. One main limitation of this technique is that the currently approved device in the United States requires a 12F sheath which requires an open femoral artery repair which obvious can be associated with significant complications. There are a huge number of unanswered questions about the use of REBOA in 2015:
1. Who are the appropriate patients in whom use may be beneficial?
2. How long can a balloon be inflated and the aorta be occluded before irreversible ischemic damage to the viscera occurs?
3. How long can the aorta be occluded before the metabolic consequences of reperfusion are lethal?
4. What is the effect on cerebral and cardiac perfusion when a REBOA is placed and afterload is acutely increased? Is it favorable or “too much”?
5. Who are the appropriate providers to place a REBOA? Only surgeons? Emergency Medicine physicians? Medics in the field?
6. How do we best train providers to place the REBOA?
7. How to we assure competency of providers?
8. Will lower profile devices make the technique more accessible and be associated with fewer complications?
Resuscitation legend John Hinds talks about the consequences of our actions in resuscitation.
He discusses resuscitative emergency thoracotomies and the philosophy and mindset required by the practitioner rather than the technicalities of how to perform it.
As John says, trying to find the fault in a wiring loom of a ZX10 is difficult. Opening a chest is not. But it has been built up to be such a heroic procedure that we're stopping people doing it.
John discusses a case and the way it was discussed in the ensuing mortality meeting. He breaks down the personalities you see in these meetings - the sycophants, supporters, the skeptics and coins the phrase #resuswankers.
The hardest part of a resuscitative thoracotomy is not making the first cut - it's dealing with the #resuswankers.
Using simulation, optimising logistics and training the team effectively John managed to change the culture in an institution. This translated into an incredible save.
Take home points include:
Prepare. Know the evidence.
Make your intentions honourable.
Do it.
Seek out the skeptics.
Never allow a wanker to bring you down.
He does this with his usual dry wit, genuine passion and refreshing modesty that have made him so popular.
To see how mating hippos and batman are of relevance, you'll have to watch the talk.
John will be dearly missed by our community and this talk shows you why.
Peter Brindley - Resuscitation: What’s the PointSMACC Conference
Resuscitation- what's the point.
Cardiopulmonary resuscitation (CPR) is unique as the only medical intervention performed on anyone without explicit contrary documentation. Therefore, CPR need to be understood in terms of societal expectations, legal mandates and professional duties. We also need to understand not just the the likelihood of survival, but also the likelihood of disability and the cost (both literally and figuratively) to patients, healthcare workers, and to an already stretched healthcare system. Even the term 'resuscitation' means different things to different people...and that's before we even wade into such terms as 'autonomy', 'paternalism' and 'patient-focused care'.
In short, doctors, nurses patients and families can no longer shy away from discussing CPR: it's time to talk. It can be a remarkable way to prevent premature death, it can also squander finite resources and be the beginning of a terrible ordeal for frail patients and frazzled families.
Sepsis kills about 7500 Australians every year. Today a new Sepsis Website launches and on the eve of World Sepsis Day, Simon Finfer discusses what sepsis is and what we can do to improve the morbidity and mortality from this familiar but enigmatic foe.
Iv fluid therapy (types, indications, doses calculation)kholeif
All what you need to know intravenous fluids, types, indications, contraindications, how to calculate fluid rate and drug dosages.
Embed code (http://www.slideshare.net/slideshow/embed_code/16138690)
Venous Thromboembolism (VTE): Recent Advances in Reducing the Disease BurdenNBCA
The National Center on Birth Defects and Developmental Disabilities, Division of Blood Disorders, hosted an important webinar for health professionals on Thursday, November 6, 2014. During this webinar, Gary Raskob, PhD, Chair of NBCA’s Medical & Scientific Advisory Board, and Dean, College of Public Health, University of Oklahoma Health Science Center, reviewed the disease burden associated with DVT/PE, and discussed strategies to reduce this burden through prevention of both first time and recurrent clots.
Weight diabetes and metabolic problems in patients taking atypical antipsycho...Alex J Mitchell
Free slide show on weight gain, diabetes and metabolic problems in those taking atypical antipsychotic medication in schizophrenia, bipolar disorder and related conditions. Image credits retained by original authors. Please give correct acknolwedgements if you present any material from here.
CORTICAL SPREADING DEPOLARISATION IN NEUROLOGICAL DISEASE – AN INTRODUCTION
By Toby Jeffcote
Cortical spreading depolarization (CSD) is a spreading loss of ion homeostasis, altered vascular response, change in synaptic architecture, and subsequent depression in electrical activity following an inciting neurological injury.
It was first described by Leão in 1944, a disturbance in neuronal electrophysiology has since been demonstrated in a number of animal studies, and recently a few human studies that examine the occurrence of this depolarizing phenomenon in the setting of a variety of pathological states, including migraines, cerebrovascular accidents, epilepsy, intracranial hemorrhages, and traumatic brain injuries. The onset of CSD has been demonstrated experimentally following a disruption in the neuronal environment leading to glutamate-induced toxicity. This initial event leads to pathological changes in the activity of ion channels that maintain membrane potential. Recovery mechanisms such as sodium-potassium pumps that aim to restore homeostasis fail, leading to osmolar shifts of fluid, swelling of the neuron, and ultimately a measurable depression in cortical activity that spreads in the order of millimeters per minute. Equally important is the resulting change in vascular response. In healthy tissue, increased electrical activity is coupled with release of vasodilatory factors such as nitric oxide and arachidonic acid metabolites that increase local blood flow to meet increased energy expenditure. In damaged tissue, not only is the restorative vascular response lacking but a vasoconstrictive response is promoted and the ischemia that follows adds to the severity of the initial injury. Tissue threatened by this ischemic response is then at elevated risk for CSD propagation and falls into a vicious cycle of electrical and hemodynamic disturbance. Efforts have been made to halt this spreading cortical depression using N-methyl-D-aspartate receptor antagonists and other ion channel blockers to minimize the damaging effects of CSD that can persist long after the triggering insult.
Celia Bradford takes us through the latest on the management of subdural haemorrhage (SDH). She covers acute SDH, chronic SDH and middle meningeal artery embolisation, a novel treatment for chronic SDH management in certain circumstances.
Andy Neill - More neuroanatomy pearls for neurocritical careSMACC Conference
Andy Neill shares some more neuroanatomy wisdom that's highly practical for anyone working with neuro emergencies. This time he covers brain herniation syndromes, hydrocephalus, extradural vs subdural haematomas, cervical spinal imaging, vertebral artery dissection and "things you read on CT reports but don't know what they mean"!
Andrew Udy talks about Brain Tissue Oxygen Monitoring:
It’s Not What You’ve Got It’s What You Do With It
The BONANZA Trial
Andrew Udy talks about the ongoing BONANZA Trial which is assessing whether an algorithm that incorporates both ICP and brain tissue oxygen (PbTO2) can improve outcomes after traumatic brain injury (TBI). Like with all monitoring, how the PbTO2 is interpreted and managed is critical and the devil is in the detail!
More on BONANZA here
More on BOOST3 here
R. Loch Macdonald, M.D., Ph.D.
Community Neurosciences Institute
Fresno, California, USA
Angiographic vasospasm and more accurately, delayed cerebral ischemia, continue to contribute to morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (SAH). It is known that angiographic vasospasm is common after SAH, occurring in two-thirds of patients. Cerebral infarctions that developed days after the SAH have been attributed to angiographic vasospasm, occuring in about a third of patients, although this has always been controversial. Angiographic vasospasm theoretically can only damage the brain by restricting blood flow but there is no easy, accurate, widely available method to measure cerebral blood flow and this is not the measurement we need. Blood flow depends on metabolic demand so what we need to know to determine if angiographic vasospasm is causing ischemia is oxygen extraction fraction in the brain tissue supplied the the spastic artery. Without this measurement, the attribution of ischemia to vasospasm is subjective. Since angiographic vasospasm is essentially the only detectable delayed phenomenon after SAH, we focus on it and apply tremendous resources to preventing or reversing the vasospasm. Undoubtedly angiographic vasospasm can cause cerebral infarctions, but it has to be severe and flow limiting. But SAH is a complex disease. There are many other causes for cerebral infarctions after SAH, the most common being due to the aneurysm repair procedure. And a given degree of vasospasm may cause infarction in a volume-depleted patient with poor collateral blood supply but not in a patient without these things. There also are hypodense brain lesions after SAH that are due to intracerebral hemorrhages. There can be hypodensities in the brain directly under usually thick SAH where the brain dies. This observation in particular supports a role for cortical spreading depolarizations/ischemia as a cause of infarction after SAH. Other macromolecular processes that are hypothesized to cause brain damage after SAH include microthromboembolism, changes in the microcirculation, delayed brain cell apoptosis and capillary transit time heterogeneity. Determining the importance of these things is hindered by the lack of an easy way to detect them in patients. It is also known that poor grade patients, who presumably have more early brain injury and ischemia than good grade patients, are more prone to delayed cerebral ischemia, suggesting increased sensitivity to secondary insults of the already injured brain. We also assume delayed neurological deterioration when attributed to vasospasm or delayed cerebral ischemia, is purely due to ischemia. While knowledge about what happens pathophysiologically after SAH is increasing, management of delayed cerebral ischemia still focuses on detecting angiographic vasospasm and then augmenting the blood pressure to improve cerebral blood flow or dilating the spastic arteries with balloons or drugs.
By Catherine Bell and Andrew Udy
Catherine Bell takes us through how to troubleshoot problems commonly encountered when looking after patients who have an external ventricular drain (EVD) in situ. Issues with using brain tissue oxygen monitors are also discussed. A highly practical session aimed at bedside clinicians.
There is no such thing as mild, moderate and severe TBI - by Andrew UdySMACC Conference
Part 2 of a debate over the classification of TBI. Andrew Udy then argues that this classification is fundamentally flawed. He discusses the issues with the Glasgow Coma Scale, and therefore the follow-on issues in TBI classification, including all the confounders to the GCS, the issues with timing of the score as well as GCS not taking baseline function or specifics subtypes of TBI into account. He makes teh argument that biomarkers may better categorise the diffuse entity we call TBI.
TBI Debate - Mild, moderate and severe categories workSMACC Conference
Andrew Chow, Intensivist with a neurosurgical background, argues that the current categorisation system for traumatic brain injury (TBI) works, and makes sense! He tackles us through the history of this system, and why it’s important to differentiate different types of TBI. The arguments in favour of this categorisation include the consistency and benefits of a universal language, the implications for triage and management, and the fact that this system has been endorsed by all major organisations
Dr Nick Little is an experienced Neurosurgeon who's looked after patients with traumatic brain injury for his whole career. Here he discusses the difficulties of prognostication following traumatic brain injury (TBI). He talks about the statistics of outcomes following mild, moderate and severe TBI and then goes on to tackle the harder topic of how we try to work out what an individual would want if they knew the spectrum of outcomes that they may face. The issues with the clinical examination findings we use to prognosticate are covered, as well as which imaging findings he finds most helpful. He also mentions the difficulties with current prognostic calculators.
Historically, when it came to brain injury, ketamine had a bad rap. Much of that dogma was dispelled in the last decade, and ketamine is now frequently used as an induction agent in acute brain injury, especially traumatic brain injury, due to it’s favorable effects on haemodynamics.
However a new application of ketamine is now being explored - whether ketamine may be able to reduce secondary brain injury.
Managing Complications of Chronic SCI by Bonne LeeSMACC Conference
20 million people around the world are living with a spinal cord injury (SCI). The medical issues they develop over the years differ to any other patient cohort.
These complications include autonomic dysreflexia, management of pressure areas, specific infections, nuanced peri-operative care and highly specific issues such as baclofen pump management and syringomyelia
Do look at the NeuroResus section on this and listen to Spinal Rehab Specialist Bonne Lee talk about this side of SCI care.
Keywords
SCI, spinal, spinal cord injury, autonomic dysreflexia, pressure areas, infection, peri-operative care, baclofen pump, syringomyelia, chronic SCI, spinal trauma, spinal rehab, incomplete SCI
Tania is a neurologist and epileptologist with expertise in continuous EEG (cEEG) and status epilepticus (SE). This talk covers what a seizure is, what status is, including focal and generalised status epilepticus.
So why do we do cEEGs for patients with suspected SE?
To confirm the diagnosis
To see if patient just post ictal or still seizing
To establish that the clinical and electric seizures have stopped
To see if burst suppression is achieved
To exclude other differential diagnoses
She makes a good argument for why cEEG is such an important tool in managing SE.
In the questions after the talk, the issue of availability of cEEG in the Australian setting was discussed. Limited montage EEGs are discussed including their pros and cons.
Stuart Browne is a Neuro Rehab specialist from Sydney. These slides accompany a talk he gave at the Brian Symposium in 2023. He discusses what "severe disability" really means.
Severe disability is more common than many realise - about 6% of the Australian population.
Stuart discusses how health is more than simply physical recovery and how it is a multidimensional construct. He covers how permanent disability doesn't necessarily equate to a poor quality of life. He also discusses the long timespan of recovery, which is often much longer than appreciated.
He specifically discusses "Locked-in Syndrome" and how the survivors have surprisingly positive self-reported health-related quality of life and well-being.
Stuart also covers how severely disabled people face various forms of discrimination.
Shree Basu is a Paediatirc Intensivist in Sydney. These slides from the Brain Symposium 2023 accompany the talk she gave. She discusses how Paediatric stroke presents, what neuroimaging is required and what interventions are available, including thrombolysis and the role of endovascular thrombectomy.
Hypertensing Spinal Cord Injury - gold standard or wacky?SMACC Conference
After spinal cord injury (SCI), there aren’t many interventions we have available that actually make a difference.
Augmenting blood pressure to increase spinal cord perfusion pressure is an attractive concept that may improve neurological outcomes following SCI. We know that hypotension can make SCI worse. Clinical studies looking at blood pressure augmentation are mostly old, retrospective and flawed in various ways.
Aiming for a MAP of > 85 for 5-7 days is recommended by guidelines but why this pressure and duration are good questions.
Hypertensive therapy is relatively safe and easy to implement but not without risk.
Tessa discusses the pros and cons, how this is managed practically and what the future may hold in this area.
Mark Weedon takes us through the increasingly utilised concept of an optimal cerebral perfusion pressure (CPPopt) for each unique patient. He discusses the background to CPPopt, including intrcranial pressure (ICP), the Monroe Kelly hypothesis, neurovascular coupling, and cerebral autoregulation in health and following brain injury. He shows how intracranial pressure is affected by intracranial compliance and how this affects ICP waveforms. Cerebral perfusion pressure in relation to the Brain Trauma Foundation guidelines is covered including management of elevated ICP (EICP). The currently recommended tiered approach to managing cerebral perfusion pressure and EICP is mentioned citing recent guidelines. He uses a clinical case of a TBI to illustrate how the CPPopt can be ascertained and used to guide therapy, including the easy to perform “MAP Challenge”. Mark also describes the Pressure Reactivity Index (PRx) and how it can be used as a target for therapy. Finally, he covers the exciting results of the preliminary COGiTATE pilot study.
Social Worker Victoria Whitfield and Bereavement councilor Louise Sayers discuss the power of words when health professionals are communicating topics around of death and serious injury with relatives and patients in critical care. They use role plays to bring theories to life.
Sepsis and Antimicrobial Stewardship - Two Sides of the Same CoinSMACC Conference
Appropriate use of antimicrobials is primarily a patient safety issue, and is the key aim of an effective antimicrobial stewardship program. We discuss the challenges in the management of a patient with sepsis, and how decision-making is usually done in the absence of effective diagnostics. Time dependent protocols and the knowledge that undertreatment of a patient with sepsis will lead to poor outcomes will lead to prescribing that may be driven by fear. Antimicrobial resistance is associated with over-use of antimicrobials but is usually not the immediate concern. Antimicrobial stewardship programs should work closely with sepsis teams to ensure that sepsis pathways are implemented across the whole hospital, and that key principles of judicious use are embedded within the clinical pathway.
Being able to prognosticate in the aftermath of a traumatic brain injury (TBI) is important as it assists with counselling patients and families. Moreover, it helps rationally allocate healthcare resources.
However, due to the heterogenous nature of TBI and variable pre brain injury patient factors and post brain injury course, this has proven to be a difficult task.
Large cohort studies have enabled improved accuracy in the prediction of 6 month mortality and unfavourable outcome.
Furthermore, many of the factors that contribute to long-term outcome have also emerged. However, it is not yet possible to use them in prediction algorithms or mathematical models.
There is emerging evidence that pre injury psychosocial and demographic factors may be of more relevance than injury severity. Moreover, that 'outcome' becomes increasingly subjective and complex as the post injury duration increases.
We end with three brief vignettes which highlight the fraught nature of long term outcome prediction.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
3. Rudyard Kipling
1865-1936
I keep six honest serving-men:
(They taught me all I knew)
Their names are What and Where
and When
And How and Why and Who
6. “The most wonderful and
satisfactory effect is the immediate
consequence of the injection.”
“The solution that was used
consisted of two drachms of
muriate, and two scruples of
carbonate of soda to sixty ounces
of water. It was at the
temperature of 108 or 110o”
“The quantity necessary to be
injected will probably be found to
depend upon the quantity of
serum lost..”
Lewins: London Medical Gazette 1832
7. “Verily sir, this is an astonishing
method of medication, and I
predict will lead to wonderful
changes and improvements in the
practice of medicine ”
Lewins: London Medical Gazette 1832
10. Thomas Graham
1805-1869
Crystalloids
“substances such as salt, sugar and
urea that could be crystallised with
ease”
Colloids (from Κθλλη, glue)
“these included substances such as
gelatin or glue, gum, egg-albumin,
starch and dextrin”
Colloid properties
“non- crystallisable, form gummy
masses when evaporated to dryness,
diffuse with extreme slowness and
would not pass through animal
membranes”
18. “I don’t care if you use dog’s piss, as long as you
use it carefully.”
Malcolm Fisher AO
What?
19. Roberts: BMJ 1998
RRD 1.68 (1.25 – 2.23)
Overall excess mortality
of 6%
(95% C.I. 3 - 9%)
24/30 studies
n=1104/1419
Favours
albumin
Favours
control
Hypovolaemia
Hypoalbuminaemia
Burns
TOTAL
20.
21. SAFE Study Investigators: NEJM 2004
2001-2003
Multicentred blinded RCT
Albumin vs saline
ICU patients
n=6997
Primary outcome: Mortality at 28d
22. Fluid volumes
Ratio of albumin to saline for first four days = 1:1.4
1 2 3 4
0
500
1000
1500
2000
Albumin
Saline
p<0.001
p<0.001
p=0.026
Day
Volumeadministered(mL)
SAFE Study Investigators: NEJM 2004
27. P=0.059
(Test for common relative risk)
Sepsis
SAFE Study Investigators: Int Care Med 2011
MVLR adjusting for baseline covariates in patients with complete data:
919/1218 (75.5%)
0.71 (0.52 – 0.97) p=0.03.
28. Caironi: New Eng J Med 2014
Multicentred open-label RCT
20% albumin (>30g/L) vs crystalloid: severe sepsis
n=1818
Primary outcome: Mortality at 28d
2008-2012
30. Choice of Colloid: Severe sepsis
0
50
100
150
200
250
300
350
400
450
OCEANIA AMERICAS ASIA NORTHERN
EUROPE
SOUTHERN
EUROPE
WESTERN
EUROPE
All
mLperperson
Albumin Starch Gelatin Dextran
Choice of Colloid: Severe sepsis
SAFE TRIPS Investigators: Crit Care 2010
32. Renal replacement therapy: 31.0 v 18.8% p=0.001
Brunkhorst: New Engl J Med 2008
P=0.48 P=0.09
Multicentred 2x2; open label RCT
10% HES 200/0.5 vs in Ringer’s lactate
n=537/600 (adaptive); severe sepsis
Primary outcome: Mortality at 28 days
2003-2005
34. Perner: New Engl J Med 2012
Multicentred blind RCT
6% HES 130/0.42 in Ringer’s acetate vs Ringer’s acetate
n=798; severe sepsis
Primary outcome: Mortality or RRT at 90d
2009-2011
35. Myburgh: New Engl J Med 2012
Multicentred blind RCT
6% HES 130/0.4 in saline vs 0.9% saline
n=7000; ICU patients
Primary outcome: Mortality at 90d
2009-2012
37. Regulatory responses
14 June 2013 (Revised 11 October 2013).
Restriction of HES in high-risk patients
24 June 2013.
“Boxed” warning against use of HES in high-risk patients
27 June 2013.
Withdrawal of registration of HES and recall of unused stock
8 April 2014
Restriction of HES in high-risk patients.
38. EU
EMA’s PRAC
recommend that
marketing
authorisations for
HES products be
suspended
UK
MHRA suspends use
of HES infusions,
recommends
crystalloids for fluid
resuscitation; supports
with position
statement by Faculty
of Intensive Care
Medicine, Intensive
Care Society, and
Royal College of
Anesthetists
USA
FDA issues Safety
Letter recommending
boxed warning for
HES solutions on
increased mortality,
severe renal injury,
and risk of bleeding
Germany
BfArM recommends
to stop using HES
products
Italy
HES products
suspended and
recalled
Ireland
Irish Board of
Medicine
recommends stop
use and distribution
of HES
Poland
Polish competent
Authorities decide to
stop use and
distribution of HES
immediately
Switzerland, France,
Spain, Czech
Republic
Recommend not to
use HES in specific
indications
Canada
Health Canada issues
advisory with
contraindications and
warnings for the use
of HES in patients with
sepsis, renal
impairment or severe
liver disease.
Australia
Australian TGA initiated risk/benefit
review, added contraindications for sepsis
and liver disease, strengthened warning
on risk of severe renal impairment and
bleeding disorders
Regulatory responses
40. Brit J Anaes / Acta Anes Scan: 2013
D Angus USA
M Antonelli ITA
A Artigas ESP
M Bauer GER
R Bellomo AUS
G Bernard USA
J Bion UK
L Brochard FRA
C Brun BuissonFRA
F Brunkhorst GER
V BumbasirevicSER
H Burchardi GER
P Caironi ITA
J Carlet FRA
J Chalmers AUS
J Chastre FRA
G Citerio ITA
D Cook CAN
J Cooper AUS
P Dellinger USA
T Evans UK
S Finfer AUS
H Flaaten NOR
R Freebairn NZ
C French AUS
D Gattas AUS
L Gattinoni ITA
H Gerlach GER
E G-BourboullisGRE
C Hartog GER
C Hinds UK
U Kaisers GER
M Levy USA
J Lipman AUS
S MacMahon AUS
D McAuley UK
S McGuiness NZ
L McIntyre CAN
M Maggorini SUI
J Mancebo ESP
J Marshall CAN
R Moreno POR
J Morgan AUS
J Myburgh AUS
C Natanson USA
R Norton AUS
D Payen FRA
A Perner DEN
V Perkovic AUS
A Pesenti ITA
V Pettilla FIN
C Putensen GER
M Quintel GER
M Ranieri ITA
K Reinhardt GER
A Rhodes UK
C Richard FRA
N RiedermannGER
I Roberts UK
G Rubenfeld CAN
F Schortgen FRA
G Sigurdsson ICE
C Sprung ISR
N Stochetti ITA
P Suter SUI
J Takala SUI
T Thompson USA
A Turner AUS
T Walsh UK
S Webb AUS
N Webster UK
T Welte GER
M White AUS
C WiedermannGER
D Young UK
R Zarychanski CAN
Brit J Anaes: On line 12 December 2013
41. Is the PRAC decision in the best interest of patients?
Increased relative risk of death ~ 6%
Increased relative risk of RRT ~ 27%
Could there be a place for HES in the future?
Only through robust, unbiased clinical trial network
Is there new evidence of safety for HES?
CRISTAL
RAFTING
BaSES
Bion: Int Care Med 2013
42. Annane: JAMA 2013
Multicentred open-label RCT
Colloids vs crystalloids
Hypotensive, hypovolaemic patients
No pre-randomisation fluids
n=2857/3010
Primary outcome: Mortality at 28d
2003-2012
43. Study or Subgroup
1.1.1 Low Risk of Bias
Yates 2014
Perner 2012
Myburgh 2012
Subtotal (95% CI)
Total events
Heterogeneity: Tau² = 0.00; Chi² = 2.07, df = 2 (P = 0.35); I² = 4%
Test for overall effect: Z = 2.12 (P = 0.03)
1.1.2 Intemediate Risk of Bias
Alavi 2012
Skhirtladze 2014
Nagpal 2012
Feldheiser 2013
Hamaji 2013
James 2011
Gondos 2010
Siegemund 2012
Guidet 2012
Subtotal (95% CI)
Total events
Heterogeneity: Tau² = 0.00; Chi² = 3.43, df = 7 (P = 0.84); I² = 0%
Test for overall effect: Z = 1.18 (P = 0.24)
1.1.3 High Risk of Bias
Du 2011
Dubin 2010
Yang 2011
Hung 2012
Lu 2012
Zhao 2013
Zhu 2011
Subtotal (95% CI)
Total events
Heterogeneity: Not applicable
Test for overall effect: Not applicable
Total (95% CI)
Total events
Heterogeneity: Tau² = 0.00; Chi² = 5.59, df = 10 (P = 0.85); I² = 0%
Test for overall effect: Z = 2.45 (P = 0.01)
Test for subgroup differences: Chi² = 0.13, df = 1 (P = 0.72), I² = 0%
Events
5
201
597
803
0
1
1
1
1
12
15
33
40
104
2
1
0
0
7
5
2
0
907
Total
104
398
3315
3817
32
81
35
26
24
56
50
117
100
521
21
9
26
41
22
80
45
0
4338
Events
2
172
566
740
0
0
0
0
0
6
14
36
32
88
2
5
0
0
12
5
4
0
828
Total
98
400
3336
3834
28
79
35
28
24
53
50
124
96
517
22
11
25
39
20
40
45
0
4351
Weight
0.2%
29.1%
59.2%
88.5%
0.1%
0.1%
0.1%
0.1%
0.8%
1.7%
4.1%
4.7%
11.5%
100.0%
M-H, Random, 95% CI
2.36 [0.47, 11.86]
1.17 [1.01, 1.36]
1.06 [0.96, 1.18]
1.10 [1.01, 1.20]
Not estimable
2.93 [0.12, 70.79]
3.00 [0.13, 71.22]
3.22 [0.14, 75.75]
3.00 [0.13, 70.16]
1.89 [0.77, 4.68]
1.07 [0.58, 1.98]
0.97 [0.65, 1.45]
1.20 [0.83, 1.74]
1.15 [0.91, 1.46]
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
1.11 [1.02, 1.20]
HES 130/0.38-0.45 Crystalloid Risk Ratio Risk Ratio
M-H, Random, 95% CI
0.01 0.1 1 10 100
Favours HES130/0.38-0.45 Favours crystalloid
HES and mortality
Increased mortality:
RR 1.11 (1.02-1.20)
NNH 53
French: unpublished (with permission)
44. HES and RRT
Study or Subgroup
1.2.1 Low RIsk of Bias
Yates 2014
Perner 2012
Myburgh 2012
Subtotal (95% CI)
Total events
Heterogeneity: Tau² = 0.00; Chi² = 2.05, df = 2 (P = 0.36); I² = 3%
Test for overall effect: Z = 2.77 (P = 0.006)
1.2.2 Intermediate Risk of Bias
Skhirtladze 2014
Lee 2011
Nagpal 2012
James 2011
Guidet 2012
Siegemund 2012
Subtotal (95% CI)
Total events
Heterogeneity: Tau² = 0.00; Chi² = 2.15, df = 5 (P = 0.83); I² = 0%
Test for overall effect: Z = 1.90 (P = 0.06)
Total (95% CI)
Total events
Heterogeneity: Tau² = 0.00; Chi² = 4.66, df = 8 (P = 0.79); I² = 0%
Test for overall effect: Z = 3.35 (P = 0.0008)
Test for subgroup differences: Chi² = 0.45, df = 1 (P = 0.50), I² = 0%
Events
4
87
235
326
1
1
1
2
21
28
54
380
Total
104
398
3352
3854
81
53
35
56
100
117
442
4296
Events
0
65
196
261
0
0
0
3
11
23
37
298
Total
98
400
3375
3873
79
53
35
53
96
124
440
4313
Weight
0.2%
24.4%
61.0%
85.7%
0.2%
0.2%
0.2%
0.7%
4.5%
8.5%
14.3%
100.0%
M-H, Random, 95% CI
8.49 [0.46, 155.59]
1.35 [1.01, 1.80]
1.21 [1.00, 1.45]
1.25 [1.07, 1.47]
2.93 [0.12, 70.79]
3.00 [0.12, 72.02]
3.00 [0.13, 71.22]
0.63 [0.11, 3.63]
1.83 [0.93, 3.59]
1.29 [0.79, 2.11]
1.44 [0.99, 2.11]
1.28 [1.11, 1.47]
HES 130/0.38-0.45 Crystalloid Risk Ratio Risk Ratio
M-H, Random, 95% CI
0.01 0.1 1 10 100
Favours [experimental] Favours [control]
Increased use of RRT
RR 1.28 (1.11-1.47)
NNH 52
French: unpublished (with permission)
45. HES- Sales Analysis- EU5
Note: Total HES Sales
irrespective of bottle size and %
Source: IMS Colloids Q2 2014 Data
6S trial
CHEST
1Reg Action- Jun’13
46. HES- Sales Analysis- China
Source: IMS Colloids Q2 2014 Data
Note: Total HES Sales irrespective of bottle size and
%
47. David Suzuki
1936-
The whole sector of public
dialogue has been badly
contaminated, deliberately, by
the corporate sector.
The whole purpose is to sow
confusion and doubt.
And it has worked.
53. Hartog Jacob Hamburger
1859-1924
‘Normal’ saline
0.9% saline is the most commonly used resuscitation fluid worldwide.
Titrational volumetric determination of osmotic
pressure in red blood cells
0.9% concentration of salt in human blood:
“Normal“ saline
Actual normality = 0.6% saine
54. Morgan: Crit Care 2008
Why does saline cause an acidosis?
n=851Cl-
154
Na+
154
Na+
154
Cl-
130
24 mEq/l
A “balanced” crystalloid will reduce extracellular SID at a rate that
precisely counteracts a dilutional alkalosis induced by weak acids.
55. Venkatesh: Anaes Int Care 2006
Why does saline cause an acidosis?
n=851
-10
-8
-6
-4
-2
0
2
4
6
8
10
0 50 100 150 200
[Hb] (g/L
SBE(mEq/L)
Need to give lots of saline
Need to give it fast
56. Model Result
Rat endotoxin infusion
+ fluid resuscitation
with NS, CSL, HES
Saline: ↓survival + worse SID
and BE than HES and CSL
Kellum: CCMed 2002
Rat CLP + HCl infusion ↑[Cl-]: hypotension Kellum: Chest 2004
Rat CLP + HCl infusion ↓BE: ↑TNF, IL-6 and IL-10 Kellum: Chest 2006
Cell culture LPS
stimulation with HCl or
lactic acid
HCl: pro-inflammatory
LA: anti-inflammatory (NO,
IL-6:IL-10 and NFKB binding)
Kellum: AJPRICP
2004
Animal data: saline / sepsis
57. Model Result
Greyhound
denervated kidney +
renal arterial hypertonic
infusion
NH4Cl > NaCl: ↓RBF + GFR Wilcox: JCI 1983
Rat isolated kidney ↑[Cl-]: ↑ pressor response to
A-II
Quilley: BJP 1983
Rat HCl infusion ↑markers of intestinal injury Pedoto: JLCM 2001
Animal data: kidney and gut
58. Model Result
Volunteers: 50ml/kg
CSL or NS over 1hr
CSL: ↓ osmolality,↑ diuresis
NS: ↑ time to micturition
Wiliams: A&A 1999
Reid Clin Sci 2003
Renal TP recipients:
CSL v NS
NS: ↑ Acidosis ↑K+ with
markers of intestinal injury
O’Malley: A&A 2005
Elderly surgical
patients: CSL v NS
NS: ↑acidosis and CO2 gap Wilkes: A&A 2001
Humans: kidney and gut
62. Yunos: JAMA 2012
Grade 2 or Grade 3 AKI Use of RRT in ICU
Log rank p=0.001
Log rank p=0.004
Single centre, sequential pilot observational trial
6m saline, gelatin, 4% albumin / 6m RL, PL-148, 20% albumin
n=760
OR 0.52
68. Shaw: Ann Surg 2012
Favours Plasmaltye
n=926
Favours Saline
n=30994
Registry, propensity-score based observational trial
Saline vs buffered salt solutions
69.
70. Saline and acid-base over time
Nested, cohort study within the SAFE study
n=691, 3 general ICUs
Bellomo: Crit Care Med 2006
Volume of fluid is predictor of acid base change
Changes are minor – alkalosis predominates
Influenced by disease severity and time
71. Plasma-‐Lyte
148®
vs
saline
n=2281
pa6ents
Primary
outcome
AKI
Secondary
outcome:
RRT,
Hospital
mortality
73. John Maynard Keynes
1883-1946
The difficulty lies, not in new
ideas, but in escaping old ones,
which ramify, for those brought up
with them, as most of us have been,
into every corner of our minds.
How?
74. The physiological fallacy
Fluid bolus therapy is self-evidently beneficial
Based on a common phenotype and surrogate variables
An inference, that cannot be measured, is made that the patient
has inadequate organ blood flow.
The second inference, that also cannot be measured, is that a fluid
bolus will restore the complexity of altered haemodynamics in a
predictable and safe fashion for the duration of the illness.
80. Mortality at 4 hours Mortality at 4 weeks
Maitland: New Eng J Med 2011
Multicentred open-label RCT
Albumin vs saline bolus vs no bolus in febrile hypotensive children
n=3141/3600
Primary outcome: Mortality at 48h
2009-2011
81. 4.6 v 2.6%: HR:1.79 (1.17 to 2.74); p=0.008
Maitland: BMC Med 2013
83. Multicentred open-label RCT
Protocolised liberal v conservative fluid strategy x 7d: ALI
n=1001
Primary outcome: Mortality at 60d
2000-2005
NHLBI ARDSnet: New Engl J Med 2006
84. Fluid volumes and outcomes
Boyd: Crit Care Med 2011
VASST study: fluid balance / CVP at 12h and 4d
n=778
85. Fluid volumes and outcomes
Bouchard: Kidney Int 2009
Dialysed Non-dialysed
Program to Improve Outcome in Acute Kidney Disease
n=618
5 US centres
86.
87. Restrictive fluid strategies
Brandstrup: Ann Surg 2003
Multicentre, single blinded RCT
Restrictive vs standard fluids, surgical patients
n=172
Perioperative complications
88. Permissive hypovolaemia in burns
Parkland
Permissive
Arlati: Resuscitation 2007
Multicentre, retrospective 2-cohort study
n=24
90. Mikkelsen: Am J RespCrit Care Med 2012
OR 4.03 (1.53–10.59), p= 0.004
FACCT follow-up: 122 of 213/406 survivors
Neuropsychological assessment at 12 months
91. Fluids are unvalidated, lethal drugs
Drug: A term of varied usage. In medicine, it refers to any
substance with the potential to prevent or cure disease or
enhance physical or mental welfare. (www.WHO.int)
92. How and why?
Myburgh: New Engl J Med 2013
Fluids should be administered with the same caution that is used
with any intravenous drug
Consider the type, dose, indications, contraindications, potential for
toxicity and cost.
Resuscitation fluids should only be used in patients with
symptomatic hypovolaemia.
93. How?
Myburgh: New Engl J Med 2013
Fluid resuscitation is a component of a complex physiological
process
Identify the fluid that is most likely to be lost and replace the fluid
lost in equivalent volumes
Consider serum osmolality and the acid-base status when
selecting a resuscitation fluid
Consider cumulative fluid balance and actual body weight when
selecting the dose of resuscitation fluid
Consider the early use of catecholamines as concomitant
treatment of shock
94. When, how and why?
Myburgh: New Engl J Med 2013
Fluid requirements change over time in critically ill patients.
The cumulative dose of resuscitation and maintenance fluids is
associated with pathological oedema that is associated with
adverse outcomes
Oliguria is a normal response to hypovolaemia and should not be
used solely as a trigger or end-point for fluid resuscitation,
particularly in the post-resuscitation period.
95. When and how?
Myburgh: New Engl J Med 2013
Fluid requirements change over time in critically ill patients.
The use of a fluid challenge in the post-resuscitation period (>24
hours) is questionable
The use of hypotonic maintenance fluids is questionable once
dehydration has been corrected.
96. Who and what?
Myburgh: New Engl J Med 2013
Specific considerations apply to different categories of patients.
Bleeding patients require control of haemorrhage and transfusion
Isotonic, buffered salt solutions are pragmatic initial resuscitation
fluids for the majority of acutely ill patients.
Consider saline in patients with hypovolaemia and alkalosis
Consider albumin during early resuscitation of patients with sepsis
97. Who and what?
Myburgh: New Engl J Med 2013
Specific considerations apply to different categories of patients.
Saline or isotonic crystalloids are indicated in traumatic brain injury
Albumin is contraindicated in traumatic brain injury
Hydroxyethyl starch should not be used in any patient population
The safety of other semi-synthetic colloids has not been established
The safety of hypertonic saline has not been established